In order to detect micrometastasis of oral squamous cell carcinoma (SCC) in regional lymph nodes, we examined a sensitive method utilizing reverse transcriptase-polymerase chain reaction (RT-PCR) for amplification of cytokeratin 19 (CK-19) mRNA.Expression of CK-19 mRNA was observed in normal oral mucosa and SCCs in primary lesions, but not in any of normal control lymph nodes by use of the RT-PCR.These results indicates that examination of the CK-19 mRNA might be useful in the detection of oral SCC micrometastases in regional lymph nodes. Moreover, sensitivity of the detection of the micrometastases was compared between the CK-19 RT-PCR and conventional histopathological examination using 40 lymph nodes obtained from 6 oral SCC patients which were macroscopically metastasis-free. As a result, CK-19 mRNA was detected in a lymph nodes which were histopathologically metastasis-positive. On the other hand, of the 39 lymph nodes which were histopathologically metastasis-negative, 35 were found not to express CK-19 mRNA but 4 were found to express CK-19 mRNA,indicating that these lymph nodes contained micrometastases which could not be detected by histopathological examination. These results demonstrate that CK-19 RT-PCR is a more sensitive method than histopathological examination for the detection of micrometastases of oral SCC in lymph nodes.